Bombesin receptor subtype‐3‐expressing neurons regulate energy homeostasis through a novel neuronal pathway in the hypothalamus

• Published in: Brain and behavior 2018-01, Vol.8 (1), p.e00881-n/a
• Main Authors: Maruyama, Minoru, Hotta, Natsu, Nio, Yasunori, Hamagami, Kenichi, Nagi, Toshimi, Funata, Masaaki, Sakamoto, Junichi, Nakakariya, Masanori, Amano, Nobuyuki, Nishida, Mayumi, Okawa, Tomohiro, Arikawa, Yasuyoshi, Sasaki, Shinobu, Kasai, Shizuo, Nagisa, Yasutaka, Habata, Yugo, Mori, Masaaki
• Format: Article
• Language: English
• Subjects: Animals; bombesin receptor subtype‐3; CHO Cells; Cricetulus; Eating - physiology; Energy; energy homeostasis; Energy Metabolism - physiology; Feeding Behavior - physiology; Homeostasis; Homeostasis - physiology; hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Male; Mice, Knockout; Nerve Tissue Proteins - metabolism; neuronal pathway; Neurons; Neurons - metabolism; obesity; Original Research; Rats; Rats, Sprague-Dawley; Receptors, Bombesin - agonists; Receptors, Bombesin - metabolism; Receptors, Somatostatin - genetics; Rodents
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.881

Objectives Bombesin receptor subtype‐3 (BRS‐3) has been suggested to play a potential role in energy homeostasis. However, the physiological mechanism of BRS‐3 on energy homeostasis remains unknown. Thus, we investigated the BRS‐3‐mediated neuronal pathway involved in food intake and energy expenditure. Materials and Methods Expression of BRS‐3 in the rat brain was histologically examined. The BRS‐3 neurons activated by refeeding‐induced satiety or a BRS‐3 agonist were identified by c‐Fos immunostaining. We also analyzed expression changes in feeding‐relating peptides in the brain of fasted rats administered with the BRS‐3 agonist. Results In the paraventricular hypothalamic nucleus (PVH), dorsomedial hypothalamic nucleus (DMH), and medial preoptic area (MPA), strong c‐Fos induction was observed in the BRS‐3 neurons especially in PVH after refeeding. However, the BRS‐3 neurons in the PVH did not express feeding‐regulating peptides, while the BRS‐3 agonist administration induced c‐Fos expression in the DMH and MPA, which were not refeeding‐sensitive, as well as in the PVH. The BRS‐3 agonist administration changed the Pomc and Cart mRNA level in several brain regions of fasted rats. Conclusion These results suggest that BRS‐3 neurons in the PVH are a novel functional subdivision in the PVH that regulates feeding behavior. As the MPA and DMH are reportedly involved in thermoregulation and energy metabolism, the BRS‐3 neurons in the MPA/DMH might mediate the energy expenditure control. POMC and CART may contribute to BRS‐3 neuron‐mediated energy homeostasis regulation. In summary, BRS‐3‐expressing neurons could regulate energy homeostasis through a novel neuronal pathway. BRS‐3 agonist mainly activated the refeeding‐sensitive PVH neurons and the refeeding‐insensitive DMH/MPA neurons. Thus, it is suggested that PVH‐BRS‐3 neruons without any typical neuroendocrine peptides are vital for feeding regulation, while MPA/DMH‐BRS‐3‐neurons might mediate the energy expenditure control. BRS‐3 neurons could regulate energy homeostasis through a novel neuronal pathway in the hypothalamus.